Personalized medicine" is a new clinical paradigm where a specific cancer therapeutic ("smart drug") is prescribed based upon the individual biology of the patient. A goal of personalized medicine is to select individual therapies based upon the correlation of proteomic profiles from diseased tissues with patient response to drug therapy. Therefore, there is a critical need for a practical tool that can generate protein expression profiles from small amounts of tissue samples collected from patients. We hypothesize that cancer patients will be treated more successfully if a correlation between proteomic profiles and drug efficacy is established and that a diagnostic test using our innovative and novel technology, Layered Protein Scanning (LPS), will be able to establish that correlation. The long-term goal of this proposal is to, by the end of Phase II, develop a clinical diagnostic tool that would be used to select and monitor patients most likely to respond to "smart drugs". To establish proof of principle, in Phase I, we will test the ability of LPS to profile Epidermal Growth Factor Receptor (EGFr) activity in head and neck squamous cell carcinoma cell lines and tissues. Specifically, we will use Layered Protein Scanning to quantitate the differences in activity of EGFr, Erkl/2, and Stat3 in: 1) Cell line samples (by comparing LPS-tissue blot with standard western blot) 2) Tissue sections of HNSCC (by comparing LPS-tissue blot to immunohistochemistry).